October 01, 2008

Last week, I gave a talk about non-patent exclusivity at ACI's FDA Boot Camp conference in Boston. The talk covered new chemical entity (5-year) exclusivity; new clinical trial (3-year) exclusivity; orphan drug exclusivity; pediatric exclusivity; and generic drug (180-day) exclusivity. You can download a copy of my slides here.

In June, I gave a talk about forfeiture of 180-day exclusivity at IIR's Generic Drugs Summit conference in Washington. The talk included a discussion of the "failure to market" forfeiture provisions, particularly the FDA's Acarbose and Granisetron decisions. You can download a copy of those slides here.

June 08, 2007

SCOTUSblog reported on Wednesday that the Supreme Court has denied Pfizer's emergency application for relief from the Federal Circuit's ruling in the Norvasc case. TheStreet.com also has an article on the Supreme Court's decision.

On Tuesday, the Federal Circuit granted Mylan's motion for summary reversal of the district court decision that had found Pfizer's Norvasc patent valid and infringed by Mylan. The Fed. Cir. also reversed and vacated a separate district court decision finding the Norvasc patent valid and infringed by Synthon. Both decisions came without opinion.

FDA Law Blog reports today that a provision of the FDA Revitalization Act will reform the citizen petition process.

The Washington Post on Monday reported on continued wrangling between the DOJ and FTC on the legality of reverse payment settlements, such as the one in Joblove.

Barr Labs announced earlier this week that Barr and Lilly agreed to dismiss their litigation over Prozac Weekly.

Kaisernetwork.org reports that the markup session for the Waxman-Schumer follow-on biologics bill has been delayed to June 20. Supporters of the bill still hope to attach it to the FDA Revitalization Act and pass it into law this year.

May 18, 2007

In a May 14 Order, the district court in D.C. denied all motions for reconsideration of its April 30 decision on Norvasc pediatric and 180-day exclusivity. FDA Law Blog has all the reconsideration briefs. Apotex and Mylan have now appealed to the D.C. Circuit.

The In Vivo Blog reports that "Democratic and Republican staffers involved in the follow-on biologics debate have reported good progress on the approval pathway and safety issues for follow-on biologics."

According to Red Herring, generic drug companies in India are very excited about the Supreme Court's recent KSR decision.

Pharmalot has this recent post on a White House trade deal favoring generic drug makers.

AP reports that the Phillippines government has petitioned to void Pfizer's Norvasc patent there.

April 30, 2007

In an April 18 decision, the FDA determined that Pfizer is entitled to six months of pediatric exclusivity on Norvasc (amlodipine besylate), that Mylan may continue to sell its generic version of Norvasc, that FDA will approve Apotex's generic Norvasc ANDA if and when the Federal Circuit issues a mandate from its March 22 decision, and that no other Norvasc generics will be approved unless Pfizer's Norvasc patent is removed from the Orange Book.

Last week, Mylan, Apotex, and Teva filed motions in the U.S. District Court for the District of Columbia challenging various aspects of the FDA's decision. This morning, in a 22-page Opinion and Order, Judge Ricardo M. Urbina denied all three motions.

Judge Urbina noted at the outset that FDA's decision is subject to the "arbitrary and capricious" standard of review, under which the court "must consider whether the agency's decision was based on a consideration of the relevant factors and whether there has been a clear error of judgment." According to the Supreme Court, "The scope of review under the arbitrary and capricious standard is narrow and a court is not to substitute its judgment for that of the agency." With this in mind, Judge Urbina addressed each of FDA's decisions:

FDA's Decision that the Effective Date of the Federal Circuit's Ruling is the Date it Issues its Mandate

Judge Urbina agreed with FDA's decision that Pfizer is entitled to pediatric exclusivity, though he used different reasoning to get there. He reasoned that because 21 USC 355a(c)(2)(B) is silent "as to the particular court which may determine the patent dispute," the January 24, 2006 Northern District of Illinois Order
in Pfizer v. Apotex triggered Pfizer's pediatric exclusivity. And, moreover, that decision "is effective and remains so during the pendency of the appeal unless the district court's judgment is stayed or until the Federal Circuit issues its mandate."

I expect Apotex will file a motion for stay very shortly.

FDA's Decision that Apotex Will Cease to Be Subject to Pfizer's Exclusivity if the Mandate Issues Before September 25, 2007

If FDA had followed its "longstanding practice to deem paragraph IV certifications as paragraph II certifications upon patent expiration," Pfizer's pediatric exclusivity period (which began upon patent expiration on March 25, 2007) would block final approval for Apotex's ANDA. However, Judge Urbina deferred to FDA's reasoning that Section 355a "manifests a clear Congressional intent that pediatric exclusivity not block the approval of an ANDA where the ANDA applicant has prevailed in the paragraph IV litigation." He concluded that "FDA's decision to exempt Apotex in light of its status as a prevailing party in challenging Pfizer's patent is reasonable and is not contrary to the language in Hatch-Waxman."

FDA Decision that Apotex is the Sole Statutory Beneficiary of the Federal Circuit's Apotex Ruling

Here, the FDA ruled that because the Federal Circuit invalidated only three claims of Pfizer's Norvasc patent and left several claims untouched, Pfizer's patent remains valid as to the remaining claims and is presumed to be properly listed in the Orange Book. Judge Urbina agreed, concluding: "Until Teva succeeds in its own patent litigation with Pfizer or until administrative or legal action completely de-lists Pfizer's patent from the Orange Book, the FDA's decision to withhold market approval for Teva's generic drug remains in effect.

This one is interesting. It sounds like Mylan meant to hold its challenge to this decision in reserve, but mistakenly filed a brief on it now. The court proceeded anyway.

Mylan argued that "nothing in the text or legislative history of the Hatch-Waxman Act indicates that generic exclusivity is forfeited upon patent expiration." Judge Urbina quickly dispensed with this argument, observing that "[u]nder Hatch-Waxman, paragraph IV certifications are no longer valid upon patent expiration" and must be changed to paragraph II certifications. At that time, the ANDA becomes eligible for immediate final approval.

Because there's so much money at stake, I would be surprised if one or more of the generic companies didn't appeal to the D.C. Circuit.

April 26, 2007

Apparently not too many companies other than Pfizer are happy with the FDA's decision last week regarding Norvasc (amlodipine besylate) exclusivity. On Monday, Mylan, Apotex, and Teva all filed motions with the U.S. District Court for the District of Columbia for injunctive relief from FDA's decision. Today, everyone filed briefs in opposition to each others' motions.

Mylan, currently the only generic on the market, is unhappy that FDA intends to approve Apotex's ANDA if and when the Federal Circuit issues a mandate from its March 22 decision. Apotex, who won that decision, wants final approval of its ANDA now--and Mylan's approval revoked. Teva, another ANDA applicant for amlodipine, argues that all ANDA applicants should be granted final approval.

Considering the expedited briefing schedule and the fact that one month of Pfizer's six-month pediatric exclusivity period has already elapsed, I would expect to see a ruling from the district court sometime next week. Given how much money is at stake in this case (Norvasc had sales of $2.5 billion in the U.S. last year), any decision is likely to be appealed.

April 18, 2007

Ever since March 22, when the Federal Circuit invalidated claims 1-3 of Pfizer's last remaining unexpired patent on Norvasc--U.S. Patent No. 4,879,303--Pfizer, Mylan and other ANDA filers have been scrambling. On March 23, Mylan, the first ANDA filer, launched its generic version of Norvasc and Pfizer responded by launching an authorized generic. On March 26, the day after the '303 patent expired, Mylan filed suit in the U.S. District Court for the District of Columbia to enjoin FDA from approving any other ANDAs for generic Norvasc. FDA asked all interested parties for their views on Pfizer's pediatric exclusivity and Mylan's 180-day exclusivity, and on April 5 FDA published those comments.

As ordered by the district court, FDA reached a decision regarding Norvasc exclusivity today. FDA's notice to the court announced: "FDA has decided not to approve ANDAs other than Mylan's at this time." According to FDA's decision letter, addressed "Dear ANDA Applicant/Holder for Amlodipine Besylate Tablets" (and submitted to the district court):

In sum, FDA has concluded:

All of the unapproved ANDAs are currently blocked by Pfizer's pediatric exclusivity.

If and when the mandate effectuating the panel's March 22 decision issues in the Apotex case, Apotex's ANDA will not be blocked by Pfizer's pediatric exclusivity.

FDA cannot determine on the current record whether other ANDAs will continue to be blocked by pediatric exclusivity at that time.

In comments submitted to FDA on March 25 and April 5, Pfizer argued that FDA could not approve any other Norvasc ANDAs at least until the Federal Circuit issues a mandate from its March 22 decision, since only then would the decision become effective. Apparently, FDA agrees.

A mandate cannot issue until disposition of a petition for rehearing or rehearing en banc, which Pfizer timely filed on April 5 (click here for Pfizer's petition). If Pfizer's petition is granted, the mandate won't issue until the Federal Circuit makes a final decision following rehearing. If Pfizer's petition is denied, the Federal Circuit will issue the mandate seven days after the decision to deny the petition.

Thus, Mylan's 180-day exclusivity period ended just two days after it began, but Mylan retains de facto generic exclusivity by virtue of Pfizer's pediatric exclusivity. In other words, Mylan is riding Pfizer's coat-tails as the sole supplier of generic Norvasc--at least until the Federal Circuit issues a mandate from its March 22 decision (when Apotex's ANDA will be granted final approval).

Moreover, it appears that even if the Federal Circuit issues a mandate before Pfizer's pediatric exclusivity expires on September 25, 2007, FDA is unlikely to approve any additional ANDAs other than Apotex's. That is because if, as seems likely, one or more of claims 4-11 of the '303 patent covers Norvasc, then the patent can remain properly listed in the Orange Book. In such a case, the remaining unapproved ANDAs will be subject to Pfizer's pediatric exclusivity. Therefore, unless another ANDA applicant successfully challenges FDA's decision, Mylan and Apotex likely will have the only Norvasc generics on the market until September 25.

April 05, 2007

A dozen companies have submitted letters in response to FDA's March 29 request for "comments from interested parties" on Norvasc (amlodipine besylate) exclusivity issues. Last week, as we reported here, FDA promised the U.S. District Court for the District of Columbia that by Wednesday, April 11, it will decide whether to approve any ANDAs for generic Norvasc besides Mylan's. Meanwhile, the district court has allowed Teva, Apotex and Mutual to intervene in the case for the limited purpose of responding, if necessary, to Mylan's motion for a temporary restraining order against FDA.